Sci-Twi, Sunset Shimmer and their friends continue their lives at CHS until one day, they get caught in a demon hunt with Sam and Dean Winchester, the hunters.

After the events at Camp Everfree, the girls come back to CHS and celebrate the day Princess Twilight Sparkle first came to their world. Only to have the party crashed by a vengeful spirit from Principal Celestia's high school days. When two men named Sam and Dean Winchester come along to kill the ghost, the girls refuse to stay out of it, seeing as it's their school!

After having no choice but to help Sam and Dean kill the ghost they were hunting, the girls realise that their home town is home to monsters and demons so they become hunters in order to save their town and their world from evil. Trained by the Winchesters and given a copy of the Lore, the Mane 7 become full-fledged hunters and travel all over town and the city to stop, kill and/or slay any demon/monster out there.